Abstract How psychedelic drugs change the activity of cortical neuronal populations and whether such changes are specific to transition into the psychedelic brain state or shared with other brain state transitions is not well understood. Here, we used Neuropixels probes to record from large populations of neurons in prefrontal cortex of mice given the psychedelic drug TCB-2. Drug ingestion significantly stretched the distribution of log firing rates of the population of recorded neurons. This phenomenon was previously observed across transitions between sleep and wakefulness, which suggested that stretching of the log-rate distribution can be triggered by different kinds of brain state transitions and prompted us to examine it in more detail. We found that modulation of the width of the log-rate distribution of a neuronal population occurred in multiple areas of the cortex and in the hippocampus even in awake drug-free mice, driven by intrinsic fluctuations in their arousal level. Arousal, however, did not explain the stretching of the log-rate distribution by TCB-2. In both psychedelic and naturally occurring brain state transitions, the stretching or squeezing of the log-rate distribution of an entire neuronal population reflected concomitant changes in two subpopulations, with one subpopulation undergoing a downregulation and often also stretching of its neurons’ log-rate distribution, while the other subpopulation undergoes upregulation and often also a squeeze of its log-rate distribution. In both subpopulations, the stretching and squeezing were a signature of a greater relative impact of the brain state transition on the rates of the slow-firing neurons. These findings reveal a generic pattern of reorganisation of neuronal firing rates by different kinds of brain state transitions.

Stretching and squeezing of neuronal log firing rate distribution by psychedelic and intrinsic brain state transitions